Mary is an obese, impoverished African-American woman living in Harlem during the 1980s. She lives with her daughter Precious, who was the product of a relationship with Carl, a married man. She also has an unnamed mother who lives nearby. Mary is cruel, selfish, loud, and aggressive. She makes heavy use of profanity. She abuses Precious and berates her grandchildren - especially the older one, a girl with Down syndrome called "Mongo". Much of her time is spent watching TV. Mary is also very lazy and would rather live off the welfare system than get a job and make money. This is because she is secretly scamming the welfare system for her own benefit.
In 1987, Precious is 16 years old, illiterate, pregnant for the second time, and still attending junior high. The principal, Mrs. Lichtenstein, is concerned about Precious' poor performance in school. She wants to move Precious to an alernative school. Mrs. Lichtenstein wants to meet with Mary, but Precious doesn't want her to.
Precious is seen at home, washing dishes for her mother. Mary asks Precious if she is going to start cooking. Mary then responds by throwing a heavy pan at Precious, knocking her out. Precious has a fantasy sequence of being at a movie premiere, where it starts to rain. The rain is actually Mary throwing water on Precious' face.
Precious is cooking dinner when Mrs. Lichtenstein comes to visit. Mrs. Lichtenstein tells Mary about the alternative school she wants to place Precious in. When the principal leaves, Mary gives in to rage and starts verbally abusing Precious, blaming her for bringing "that white bitch" over. She claims that visitors will interfere with her welfare checks. As Mary gets angrier, her complaints get worse. Mary screams that school is useless for Precious, makes fun of Precious' weight problem (despite being quite heavy herself), and even states that Precious should have been aborted. Precious angrily throws a shoe downstairs, landing near Mary. Mary responds by chasing Precious to her room and beating her.
Precious attends the alternative school with her teacher. She has her ups and downs there. (One "down" involves a flashback of Mary calling Precious "a dumb bitch".)
But this does not please Mary. Mary opposes the idea of Precious attending the alternative school. Then she demands that her daughter cook for her. Precious cooks a meal of pigs' feet. However, she forgot to make collard greens. Mary is furious, and she forces Precious to eat the meal, claiming Precious "fucked it up". Precious is not hungry, but she ends up eating the meal. While eating the pigs' feet and watching an old Italian film with Mary, Precious sees herself in the movie with her mother taunting her with "mangia, puttana".
Soon after, Precious goes the welfare office. She meets a social worker named Mrs. Weiss. Precious tells her about her daughter Mongo. This involves a scene with Mary pretending to be nice to Mongo, only to be mean to her afterwards. Precious then reveals that her father impregnated her twice. She also reveals that she delivered Mongo while lying on the floor as Mary was kicking her on the head. There are also implications that Mary herself had molested Precious.
The alternative school is having a good effect on Precious. On a class trip to the museum, Precious realizes that she wants to teach her babies, and that she will keep the undelivered baby. Eventually, Precious goes into labor and delivers her second child, Abdul.
Precious brings Abdul home to Mary. This time Mary has had it with Precious. Mary asks to hold Abdul, but then throws him on the floor and throws a glass at Precious. Because Precious exposed her wrongdoing, resulting in her welfare being cut off, Mary claims that Precious ruined her life, and the two fight. Precious decides to run away with Abdul. In the process, Mary throws a TV set at them, which the two avoid. Once Precious and Abdul are gone, Mary collects the TV and brings it back upstairs. When she tries to turn the TV on, it does not respond - Mary had destroyed her own TV. Not long afterwards, Mary tears up Precious' room.
Precious ends up in a halfway house. Her literacy has improved dramatically and she is rewarded for it. One day, Mary visits Precious and tells her that Carl has died of AIDS. Precious fears that she and Abdul might have come down with the HIV virus. Precious gets tested for the virus. While Abdul is fine, Precious finds out she is HIV positive.
Mary and Precious meet one last time with Mrs. Weiss. Mary reveals that Carl molested Precious and that she blames Precious for him leaving. Mary expresses interest in reuniting the family, including Mongo. Precious refuses, and decides to take her kids and leave Mary forever. Once Precious leaves, Mary never sees her again.
Mary appears one last time in The Kid. Precious has died of AIDS several years after being diagnosed. Not long after Precious' funeral, Mary dies as well.